Hexane → 6-[2-(4-Methyl-oxazole-5-carbonyl)-phenyl]-hept-2-en-4-ynoic acid ethyl ester

HRID 563942Notes

Reaction equation

HRID 563942 reaction equation
[CH3:1][C:2]1[N:3]=[CH:4][O:5][C:6]=1[C:7]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[CH:15]([CH3:18])[C:16]#[CH:17])=[O:8].C(N(CC)C(C)C)(C)C.[CH2:28]([O:30][C:31](=[O:35])[CH:32]=[CH:33]I)[CH3:29].CCCCCC>C1COCC1.CCOC(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.CC(C)=O>[CH2:28]([O:30][C:31](=[O:35])[CH:32]=[CH:33][C:17]#[C:16][CH:15]([C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=1[C:7]([C:6]1[O:5][CH:4]=[N:3][C:2]=1[CH3:1])=[O:8])[CH3:18])[CH3:29]

Participants

10

Reactant 4

HCID 8058HexaneHCID 81531DiisopropylethylamineHCID 4184066(Z)-Ethyl 3-iodoacrylateHCID 17748172(4-Methyl-oxazol-5-yl)-[2-(1-methyl-prop-2-ynyl)-phenyl]-methanone

Product 1

HCID 731525776-[2-(4-Methyl-oxazole-5-carbonyl)-phenyl]-hept-2-en-4-ynoic acid ethyl esterYield 63%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 180AcetoneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 300 mg (1.25 mmol, 1.0 eq) of alkyne 11b in 3.0 mL of dry THF was stirred in a 10 mL round bottom flask at room temperature under argon. To this solution was added 650 μL (3.75 mmol, 5.0 eq) of N,N-diisopropylethylamine followed by 340 mg (1.50 mmol, 1.2 eq) of 3-Iodo-acrylic acid ethyl ester. This solution was then sparged with argon for 10 minutes, at which point 44 mg (0.063 mmol, 0.05 eq) of PdCl2(PPh3)2 and 12 mg (0.063 mmol, 0.05 eq) of CuI were added at once and the solution was stirred at room temperature until the reaction was complete by TLC (3:1 hexane:acetone, Rf=0.30). Upon completion (˜4 hours) the reaction was diluted with EtOAc and washed with 1.0 M HCl. The aqueous layer was then extracted twice with EtOAc. The combined organic fractions were then washed with saturated NaHCO3 and brine and then dried over MgSO4. Purification via silica gel flash chromatography (hexane/EtOAc) yielded 252 mg (63%) of 11c as a pale brown oil, Rf 0.47 (1:1 hexane:EtOAc). 1H-NMR (500 MHz, CDCl3): 7.92 (1H, s), 7.87 (1H, d, J=7.9 Hz), 7.56 (1H, dt, J=7.8 Hz, 1.2 Hz), 7.41 (1H, d, J=7.6 Hz), 7.35 (1H, t, J=7.6 Hz), 6.11 (1H, dd, J=11.5 Hz, 2.4 Hz), 6.04 (1H, d, J=11.5 Hz), 4.35 (1H, dq, J=7.1 Hz, 2.2 Hz), 4.21 (2H, q, J=7.1 Hz), 2.39 (3H, s), 1.57 (3H, d, J=7.1 Hz), 1.27 (3H, t, J=7.1 Hz). 13C-NMR (500 MHz, CDCl3): 185.43, 164.92, 152.18, 147.04, 145.37, 142.09, 136.11, 131.86, 129.00, 128.44, 128.35, 126.69, 123.28, 105.40, 79.35, 60.52, 29.88, 24.64, 14.42, 14.18. IR (cm−1): 2976 (m), 2213 (w), 1719 (s), 1653 (s), 1603 (m), 1579 (s), 1384 (m), 1355 (m), 1291 (m), 1183 (vs), 905 (s). HRMS (EI) calcd. for C20H19NO4: 337.1314. found: 337.1322.

Workup

  1. additionwere added at once and the solution
  2. washwashed with 1.0 M HCl
  3. extractionThe aqueous layer was then extracted twice with EtOAc
  4. washThe combined organic fractions were then washed with saturated NaHCO3 and brine
  5. dry with materialdried over MgSO4
  6. customPurification via silica gel flash chromatography (hexane/EtOAc)

Sources & evidence

ORD record
ord-dd6459db24f34649b441d0b3e85cd26f
Source dataset
uspto-grants-2011_11
Patent number
US08067583B2

Reaction notes

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